Mechanism of Jinteng Qingbi granules in the treatment of rheumatoid arthritis using metabolomics analysis.

This study investigated the differential metabolites after rheumatoid arthritis (RA) rats were treated with Jinteng Qingbi granules. Collagen-induced arthritis rats were divided into three groups, namely normal group, model group, and Jinteng Qingbi granules group. Serum compounds were identified, annotated, and classified using metabolomics to explain the physicochemical properties and biological functions. The metabolites were screened using univariate and multivariate statistical analyses. There were differences in serum metabolites between RA and normal rats; Jinteng Qingbi granules improved RA and recovered the metabolite levels to normal. Compared to the normal group, 51 differential ions were screened, and 108 ions were changed in the Jinteng Qingbi granules group compared to the RA model. Eight metabolites were upregulated in the RA model group compared to the normal group, whereas 10 metabolites were downregulated. Treatment with Jinteng Qingbi granules increased the levels of 12 metabolites such as cinnamate and decreased the levels of 16 metabolites such as allamandin in the RA model. Differential ion enrichment was mainly related to the histidine metabolic pathway in amino acid metabolism. Jinteng Qingbi granules resulted in improvements in the RA model, which were mainly associated with lipids and lipid-like molecules, organic acids, and derivatives, providing a new possibility and basis for screening biomarkers for the diagnosis and treatment of RA.

Lipid Receptor G2A-Mediated Signal Pathway Plays a Critical Role in Inflammatory Response by Promoting Classical Macrophage Activation.

Macrophage polarization is a dynamic and integral process in tissue inflammation and remodeling. In this study, we describe that lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in controlling inflammatory macrophage (M1) polarization in rodent experimental autoimmune encephalomyelitis (EAE) and in monocytes from multiple sclerosis (MS) patients. Specific inhibition of Lp-PLA2 led to an ameliorated EAE via markedly decreased inflammatory and demyelinating property of M1. The effects of Lp-PLA2 on M1 function were mediated by lysophosphatidylcholine, a bioactive product of oxidized lipids hydrolyzed by Lp-PLA2 through JAK2-independent activation of STAT5 and upregulation of IRF5. This process was directed by the G2A receptor, which was only found in differentiated M1 or monocytes from MS patients. M1 polarization could be inhibited by a G2A neutralizing Ab, which led to an inhibited disease in rat EAE. In addition, G2A-deficient rats showed an ameliorated EAE and an inhibited autoimmune response. This study has revealed a mechanism by which lipid metabolites control macrophage activation and function, modification of which could lead to a new therapeutic approach for MS and other inflammatory disorders.

Seminaphthorhodafluor Derivatives Bridged Periodic Mesoporous Organosilicas for Detection of Cu2.

Seminaphthorhodafluor (SNARF) Schiff base (SNARF-SB) bridged periodic mesoporous organosilicas (SSPMOs) with "turn-on" fluorescence enhancement for sensing Cu2+ were synthesized via a template-directed co-condensation method. Small-angle x-ray scattering (SAXS) patterns, high resolution transmission electron microscope (HRTEM) images, and N2 adsorption-desorption isotherms indicated the presence of mesoporous structure in the SSPMOs. FT-IR spectra and 29Si MAS NMR data confirmed the successful incorporation of bridged organic groups in the framework of SSPMOs. The luminous properties that SSPMOs had a selective response to Cu2+ were investigated by UV-Vis absorption spectroscopy and fluorescence spectroscopy. The limit of detection (LOD) was 5.1 × 10-7 M and binding stoichiometry was determined 1:1 between SNARF-SB and Cu2+. The fluorescence enhancement of SSPMOs towards Cu2+ was induced by ring-opening of the spirolactam in SNARF-SB in framework of SSPMOs, which was confirmed by FT-IR spectra of SNARF-SB with Cu2+. Moreover, SSPMOs have improved fluorescence lifetimes compared with that of SNARF-SB. Therefore, SSPMOs can be a progressive chemical sensor for Cu2+ due to its high selectivity, recyclability, and stability.

An electrochemiluminescence resonance energy transfer biosensor based on CDs/PAMAM/rGO nanocomposites and Au@Ag2S nanoparticles for PML/RARα fusion gene detection.

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.

Investigation of Excited-State Intramolecular Proton Transfer and Structural Dynamics in Bis-Benzimidazole Derivative (BBM).

The bis-benzimidazole derivative (BBM) molecule, consisting of two 2-(2'-hydroxyphenyl) benzimidazole (HBI) halves, has been synthesized and successfully utilized as a ratiometric fluorescence sensor for the sensitive detection of Cu2+ based on enol-keto excited-state intramolecular proton transfer (ESIPT). In this study, we strategically implement femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, aided by quantum chemical calculations to investigate the detailed primary photodynamics of the BBM molecule. The results demonstrate that the ESIPT from BBM-enol* to BBM-keto* was observed in only one of the HBI halves with a time constant of 300 fs; after that, the rotation of the dihedral angle between the two HBI halves generated a planarized BBM-keto* isomer in 3 ps, leading to a dynamic redshift of BBM-keto* emission.

Critical roles of the E3 ubiquitin ligase FBW7 in B-cell response and the pathogenesis of experimental autoimmune arthritis.

Proper regulation of B-cell function is essential for effective humoral immunity and maintenance of immune tolerance. Here, we found that FBW7 (F-box/WD40 repeat-containing protein 7) is highly expressed in germinal centre B and B1 cells, and confirmed that it has an intrinsic role in maintaining homeostasis of mature B cells and B-1 cells. FBW7 deletion led to an impairment of antibody response, and although germinal centre formation was not affected, antibody class-switch recombination and affinity maturation processes were defective. Likewise, memory immune response was severely impaired. Moreover, FBW7 ablation ameliorated the pathogenesis of an autoimmune disease model, collagen-induced arthritis, by reducing the production of anti-collagen II autoantibodies. Taken together, these data suggest that FBW7 may be an attractive target for developing new therapeutics for the treatment of autoimmune diseases.

Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis.

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Although much research has focused on its regulation and function of GC B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that EAE is exacerbated in LysM Cre+/- Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4+ Th17 cell response. In addition, LPS-induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the interleukin-6 (Il-6) promoter in macrophages, leading to a suppressed transcription of Il-6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il-6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease.

Regulation of humoral immune response by HIF-1α-dependent metabolic reprogramming of the germinal center reaction.

Hypoxia-inducible factor-1α (HIF-1α) has been implicated in the regulation of many genes responsible for aerobic glycolysis; however, the role of HIF-1α in B-cell metabolism has not been well defined. Here, we analyzed patterns of gene expression and oxygen consumption rates in B-cell subpopulations from humans and mice and described a model of HIF-1α-mediated B-cell metabolic reprogramming during the germinal center (GC) reaction. Importantly, we found that HIF-1α was highly expressed in GC B-cells, and HIF-1α deficiency in B-cells impaired a functional GC reaction, resulting in defective class-switch recombination and generation of high-affinity plasma cells. These results identified an important role of HIF-1α in regulating humoral immunity through metabolic reprogramming during the GC response. This newly discovered metabolic character of GC B-cells will advance our understanding of GC biology and B-cell lymphomagenesis.

Luteolin attenuates cancer cell stemness in PTX-resistant oesophageal cancer cells through mediating SOX2 protein stability.

Cancer drug resistance is a formidable obstacle that enhances cancer stem-like cell properties, tumour metastasis and relapse. Luteolin (Lut) is a natural flavonoid with strong antitumor effects. However, the underlying mechanism(s) by which Lut protects against paclitaxel-resistant (PTX-resistant) cancer cell remains unknown. Herein, we found that Lut significantly attenuated the stem-like properties of PTX-resistant cancer cells by downregulating the expression of SOX2 protein. Additionally, further study showed that Lut could inhibit the PI3K/AKT pathway to decrease the phosphorylation level of AKT(S473) and UBR5 expression, which is an ubiquitin E3 ligase that promotes SOX2 degradation. In addition, Lut also inhibited PTX-resistant cancer cell migration and invasion by blocking epithelial-mesenchymal transition (EMT). Importantly, Lut inhibited the tumorigenic ability of oesophageal PTX-resistant cancer cells and showed no obvious toxicity in vivo. Thus, Lut has potential as a promising agent for drug-resistant oesophageal cancer therapy.

An "off-on-off" fluorescence chemosensor for the sensitive detection of Cu2+ in aqueous solution based on multiple fluorescence emission mechanisms.

A new organosiloxane precursor ((E)-3-hydroxy-4-((2-(2-hydroxy-4-(3-(3-(triethoxysilyl)propyl)ureido)benzoyl)hydrazono)methyl)phenyl(3-(triethoxysilyl)propyl)carbamate, hereinafter referred to as AHBH-Si) and tetraethylorthosilicate (TEOS) were mixed as the mixed Si source, and bridged periodic mesoporous organic silica (AHBH-PMOs) nanoparticles were obtained through the co-condensation reaction. AHBH-PMO nanoparticles possess mechanisms of "Aggregation Induced Emission" (AIE) and "Intramolecular Charge Transfer" (ICT), which originate from the molecular structure of AHBH having "C[double bond, length as m-dash]N" bond, ortho hydroxyl groups, etc.. Therefore, the optical properties of AHBH are excellent with respect to the solvent effect and enhanced fluorescence. For hybrid materials, the silica framework provides a rigid environment that restricts the rotation of AHBH, thereby turning on the fluorescence of AHBH due to the regulation by the AIE effect. In particular, AHBH-PMOs are no longer restricted by organic solvents and could really achieve the response to Cu2+ with high sensitivity and selectivity in aqueous solutions of a wide pH range. In addition, the detection limit is as low as 3.26 × 10-9 M. Methods such as Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry have shown the coordination interaction between AHBH and Cu2+. The Gaussian 09 software of density functional theory to calculate the reducing changes of energy gaps among AHBH and AHBH-Si before and after the addition of Cu2+ showed that coordination interaction exists in the system. These results indicate that AHBH-PMO hybrid materials have potential applications in the field of environmental monitoring.

Luteolin combined with low-dose paclitaxel synergistically inhibits epithelial-mesenchymal transition and induces cell apoptosis on esophageal carcinoma in vitro and in vivo.

Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial-mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway-mediated activation of mitochondrial apoptotic pathway.

DLL3 is regulated by LIN28B and miR-518d-5p and regulates cell proliferation, migration and chemotherapy response in advanced small cell lung cancer.

Delta-like protein 3 (DLL3) has been reported as a biomarker in various human tumors. However, the biological function and mechanism of it in advanced small cell lung cancer (SCLC) is rarely reported. This study was devised innovatively to explore the role of DLL3 in the progression of SCLC. Immunohistochemistry (IHC) analysis was used to examine DLL3 expression in paraffin-embedded SCLC tumor samples. Upregulation of DLL3 reduced chemotherapy sensitivity. Kaplan-Meier analysis was used to analyze the progression-free survival or overall survival of SCLC patients with high or low level of DLL3. The negative association between DLL3 expression and the PFS or OS rate of SCLC patients was identified. Relative high level of DLL3 was determined in SCLC cell lines by using qRT-PCR analysis. Loss-of function assays were performed to detect the biological functions of the silencing of DLL3 in SCLC. As a result, silencing of DLL3 led to the proliferative and migratory inhibition of SCLC cells and reversed EMT process. Mechanistically, DLL3 mRNA was stabilized by the RNA-binding protein lin-28 homolog B (LIN28B). Further mechanism investigation revealed that LIN28B and DLL3 are two downstream targets of miR-518d-5p. Finally, rescue assays demonstrated that LIN28B and miR-518d-5p could regulate DLL3-mediated cell proliferation and migration. Collectively, our present study revealed a novel molecular pathway in SCLC, which providing a new insight in exploring the therapeutic strategy for SCLC.

Prognostic role of the advanced lung cancer inflammation index in cancer patients: a meta-analysis.

BACKGROUND: Inflammation plays a critical role in the development and progression of cancers. The advanced lung cancer inflammation index (ALI) is thought to be able to reflect systemic inflammation better than current biomarkers. However, the prognostic significance of the ALI in various types of cancer remains unclear. Our meta-analysis aimed to comprehensively investigate the relationship between the ALI and oncologic outcomes to help physicians better assess the prognosis of cancer patients. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated and pooled from the included studies. Furthermore, a sensitivity analysis was performed to evaluate the reliability of the articles. Finally, Begg's test, Egger's test, and the funnel plot were applied to assess the significance of publication bias. RESULTS: In total, 1736 patients from nine studies were included in our meta-analysis. The median cutoff value for the ALI was 23.2 (range, 15.5-37.66) in the analyzed studies. The meta-analysis showed that there was a statistically significant relationship between a low ALI and worse overall survival (OS) in various types of cancer (HR = 1.70, 95% CI = 1.41-1.99, P < 0.001). Moreover, results from subgroup meta-analysis showed that the ALI had a significant prognostic value in non-small cell lung cancer, small cell lung cancer, colorectal cancer, head and neck squamous cell carcinoma, and diffuse large B cell lymphoma (P < 0.05 for all). CONCLUSIONS: These results showed that a low ALI was associated with poor OS in various types of cancer, and the ALI could act as an effective prognostic biomarker in cancer patients.

Increased circular RNA hsa_circ_0012673 acts as a sponge of miR-22 to promote lung adenocarcinoma proliferation.

Recent reports have indicated that circular RNA (circRNA) may regulate Lung adenocarcinoma (LAC) development. Our previous studies showed that hsa_circ_0012673 was up-regulated in a circRNA microarray. However, its expression level in LAC has not been verified, and the underlying molecular mechanisms in LAC are unknown. In this study, we found that the expression of hsa_circ_0012673 was up-regulated in LAC tissues compared to pair-matched adjacent non-tumor tissues (P = 0.0079), and that the expression level was associated with tumour size (P = 0.015). Furthermore, hsa_circ_0012673 was primarily localized in the cytoplasm and promoted cell proliferation of LAC cells by sponging miR-22, which targeted erb-b2 receptor tyrosine kinase 3 (ErbB3) in LAC. Hsa_circ_0012673 promotes LAC proliferation by suppressing miR-22, which targets ErbB3.

Therapeutic Effects of a Long-Acting Cholinergic Receptor Blocker, Tiotropium Bromide, on Asthma.

BACKGROUND The aim of this study was to evaluate the therapeutic effects of tiotropium bromide on asthma. MATERIAL AND METHODS A total of 160 patients with moderate persistent asthma were randomly divided into 4 groups (n=40): the 3 control groups were given fluticasone propionate aerosol (group A), salmeterol-fluticasone propionate inhalant (group B), and tiotropium bromide inhalation powder combined with salmeterol-fluticasone propionate inhalant (group C), respectively, and the experimental group received tiotropium bromide inhalation powder combined with fluticasone propionate aerosol (group D) and salbutamol was used to relieve symptoms when necessary. RESULTS After 8 weeks of treatment, the pulmonary function of group D, which was significantly better than those of group A (P<0.05), was similar to those of groups B and C (P>0.05). Group D had significantly better asthma control test scores and nighttime symptom scores than in group A (P<0.05), without significant differences from those of group B or group C (P>0.05). The number of times salbutamol was used to alleviate symptoms was significantly different (P<0.05) between group D and group A (P<0.05), as well as between group C and group D (P<0.05). Groups D and B had similar results (P>0.05). IL-13 levels in induced sputum had significant differences (P<0.05). The levels in group D, which were higher than those of groups A and B (P<0.05), were similar to those of group C (P>0.05). CONCLUSIONS Tiotropium bromide combined with fluticasone propionate improved the respiratory function and quality of life, and is a new therapy for moderate, persistent asthma.

Progress in research on the role of circular RNAs in lung cancer.

BACKGROUND: Circular RNA (circRNA), as a covalently closed circular RNA molecule, is widely present, which is recognized as a competing endogenous RNA. A large number of differentially expressed circRNAs have been identified and are recognized as potential biomarkers for the diagnosis of tumors. MAIN BODY: CircRNAs play an important role in the regulation of cell signaling pathways. The main biological functions of circRNAs include acting as miRNA sponges, regulating the transcription of the parental genes, and acting as adapters to regulate the interactions between proteins and encoding proteins. Compared with normal tissues, there are differentially expressed circRNAs in lung cancer tissue, and the expression levels of circRNAs are correlated with clinicopathological features of lung cancer. Their roles in pathway regulation are described, and the diagnostic and prognostic values are further evaluated. CONCLUSION: In lung cancer, circRNAs participate in the proliferation, migration, and invasion, acting as a competitive endogenous RNA. Differentially expressed circRNAs may serve as non-invasive diagnostic markers for lung cancers. Further investigation of the roles of circRNAs in the pathogenesis and regulatory pathways is conducive to the development of novel approaches for the diagnosis and accurate treatment of lung cancers.

A tricorn-rhodamine fluorescent chemosensor for detection of Co2+ ions.

A novel chemosensor TrisRh based on tris(2-aminoethyl)amine and rhodamine 6G is designed and synthesized as a fluorescence turn-on probe for Co2+ ions that is paramagnetic with a property of quenching fluorescence. Rhodamine spirolactam forms are nonfluorescent, whereas, ring-opening of corresponding spirocyclic induced by Co2+ results in strong fluorescence emission. Upon the addition of Co2+ ions, TrisRh can display significant enhancements in absorbance and fluorescence intensity as well as evident colorific transformation, which can be perceived by the naked eye. The association stoichiometry of TrisRh to Co2+ ions was inferred to be 1:1 through Job's plot and electrospray ionization mass spectrometry analysis. The binding model was speculated from Fourier transform infrared spectra and 1 H-nuclear magnetic resonance technologies. Significantly, the limit of detection was determined to be as low as 1.22 nmol. Furthermore, TrisRh can exhibit robust anti-jamming ability against other interference metal ions.

Deficiency of autophagy in dendritic cells protects against experimental autoimmune encephalomyelitis.

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the immune system. DCs present antigens to CD8 and CD4 T cells in the context of class I or II MHC. Recent evidence suggests that autophagy, a conserved intracellular degradation pathway, regulates class II antigen presentation. In vitro studies have shown that deletion of autophagy-related genes reduced antigen presentation by APCs to CD4 T cells. In vivo studies confirmed these findings in the context of infectious diseases. However, the relevance of autophagy-mediated antigen presentation in autoimmunity remains to be elucidated. Here, we report that loss of autophagy-related gene 7 (Atg7) in DCs ameliorated experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-mediated mouse model of multiple sclerosis, by reducing in vivo priming of T cells. In contrast, severity of hapten-induced contact hypersensitivity, in which CD8 T cells and NK cells play major roles, was unaffected. Administration of the autophagy-lysosomal inhibitor chloroquine, before EAE onset, delayed disease progression and, when administered after the onset, reduced disease severity. Our data show that autophagy is required in DCs for induction of EAE and suggest that autophagy might be a potential target for treating CD4 T cell-mediated autoimmune conditions.

Ratiometric fluorescent nanosensors for copper(II) based on bis(rhodamine)-derived PMOs with J-type aggregates.

By using pentyl-linked bis(rhodamine)-derived tetra-siloxane (PRh-Si4 ) as the organosilica precursor, highly ordered PRh-bridged periodic mesoporous organosilicas (PRhPMOs) were prepared. When excited at λ=500 nm, the PRhPMO suspension that contained metal ions showed two separate emission peaks at λ=550 and 623 nm. The first peak, located at λ=550 nm, was due to ring-opening of the spiro structure in the rhodamine moiety and the second, located at λ=623 nm, originated from fluorescent aggregates of the PRh units embedded in the silica framework of the PRhPMO. By using the different intensity ratios of the two fluorescence signals (FI550/623), PRhPMOs could be used as turn-ON type fluorescent ratiometric chemosensors for Cu(2+). Furthermore, based on the single-exciton theory, it was deduced that the fluorescent aggregates formed were of the J-type and had a coplanar configuration. Consequently, PRhPMOs display a longer fluorescence lifetime and greater fluorescent quantum yield than the respective monomers dissolved in solution, which is consistent with the experimental results.

Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via MET/STAT3/Akt Pathway.

Background: Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. However, the underlying molecular mechanism of anlotinib mediates cisplatin (DDP) resistance in NSCLC remains unclear. Methods: Cell viability was assessed by the cell counting kit 8 assay. Cell proliferation, migration, and invasion were determined using the colony formation assay and transwell assay. The mRNA expression levels of mesenchymal-epithelial transition factor (MET) and myeloid cell leukemia-1 (MCL-1) were measured by quantitative real-time PCR. Protein expression levels of MET, MCL-1, and STAT3/Akt pathway-related markers were examined using western blot analysis. Results: Our data showed that anlotinib inhibited the DDP resistance of NSCLC cells by regulating cell proliferation and metastasis. Moreover, MET and MCL-1 expression could be decreased by anlotinib treatment. Silencing of MET suppressed the activity of the STAT3/Akt pathway and MCL-1 expression. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway). Conclusion: Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.